The de novo design of α-helical peptides for supramolecular self-assembly

One approach to designing de novo proteinaceous assemblies and materials is to develop simple, standardised building blocks and then to combine these symmetrically to construct more-complex higher-order structures. This has been done extensively using beta-structured peptides to produce peptide fibres and hydrogels. Here, we focus on building with de novo alpha-helical peptides. Because of their self-contained, well-defined structures and clear sequence-to-structure relationships, alpha helices are highly programmable making them robust building blocks for biomolecular construction. The progress made with this approach over the past two decades is astonishing and has led to a variety of de novo assemblies, including discrete nanoscale objects, and fibrous, nanotube, sheet and colloidal materials. This body of work provides an exceptionally strong foundation for advancing the field beyond in vitro design and into in vivo applications including what we call protein design in cells.